PROJECT SUMMARY Optimal body hydration is considered imperative to preserving vocal health by many experts in the field. To this end, minimizing dehydration and increasing hydration is often recommended to prevent voice problems and as treatment for ongoing problems. The presumption underlying this recommendation is that dehydration induces adverse pathological and biomechanical changes to the vocal folds, and that speakers will develop maladaptive, phonotraumatic behaviors to compensate. Due to the prevalence of phonotraumatic voice problems, initiating hydration treatments has become a common, unfounded clinical recommendation. The critical, missing links in this argument are the absence of data demonstrating adverse pathobiological and biomechanical effects of dehydration, and a realistic model to test these data endpoints. A realistic model should have intact homeostatic mechanisms that regulate hydration in vivo and be amenable to rigorous control of hydration state. A rabbit animal model that is dehydrated systematically meets these requirements. The first goal of this proposal is to quantify the adverse pathobiological and biomechanical sequelae of acute dehydration. Systemic and surface dehydration will be induced to physiologically-relevant levels that have been shown to induce voice changes in human speakers. The distinct effects of systemic and surface dehydration will be quantified in young and old rabbits in order to delineate the influence of route of dehydration, as well as age, on fluid homeostasis. The second goal of this proposal is to establish whether systemic and surface rehydration can reverse adverse vocal fold changes induced by dehydration in young and old rabbits. The third goal of this proposal is to establish differential effects of chronic systemic and chronic surface dehydration in young and old rabbits. Chronic dehydration might not only increase impairments that are observed in acute dehydration, but may also reveal mechanisms of degeneration not identified in the first two goals. Pathobiological and biomechanical endpoints will include proton density MRI as a non-invasive measure of vocal fold hydration state, and histological, cellular, molecular, and biomechanical assessment of the vocal folds following dehydration and rehydration. By combining cellular, molecular, structural, and functional techniques, this comprehensive proposal seeks to shed fundamental insight into the effects of altered hydration state on vocal fold fluid, epithelium, lamina propria and muscle tissue so that validated scientific recommendations can be made on the adverse effects of dehydration and the therapeutic benefits of hydration.